Canakinumab in adults with steroid-refractory pyoderma gangrenosum

A. G.A. Kolios, J. T. Maul, B. Meier, K. Kerl, C. Traidl-Hoffmann, M. Hertl, D. Zillikens, M. Röcken, J. Ring, A. Facchiano, C. Mondino, N. Yawalkar, E. Contassot, A. A. Navarini, L. E. French


BACKGROUND: Pyoderma gangrenosum (PG) is a rare, neutrophilic, ulcerative skin disease that is difficult to treat, especially when unresponsive to steroids.\n\nOBJECTIVES: To determine whether canakinumab is an effective and safe treatment in PG.\n\nMETHODS: Five adult patients with clinically and histologically confirmed steroid-refractory PG were enrolled in this prospective open-label study. They received canakinumab 150 mg subcutaneously at week 0 with an optional 150 mg at week 2 in case of an inadequate response [Physician's Global Assessment (PGA) ≥ 2], and an optional 150-300 mg at week 8 depending on PGA. The primary clinical end point was clinical improvement (PGA at least -1 from baseline) and/or complete remission (PGA 0 or 1) at week 16. Real-time quantitative polymerase chain reaction was performed on skin samples to quantify cytokine mRNA levels.\n\nRESULTS: Interleukin (IL)-1β and its known target genes IL6, CXCL8 and IL36A were significantly increased in lesional skin of PG. Under canakinumab therapy, four of five patients showed a decrease in target-lesion size, PGA and Dermatology Life Quality Index (DLQI), and three of five achieved complete remission. The mean diameter of target lesions decreased from 4·32 ± 2·6 cm at visit 1 to 0·78 ± 1·3 cm at visit 7 (P = 0·03). Mean DLQI decreased from 15 ± 5 at visit 1 to 8 ± 4 by visit 7 (P = 0·01). Adverse effects were reported in two patients: fatigue in one and worsening of disease at a nontarget lesion in the other.\n\nCONCLUSIONS: Our data indicate that IL-1β plays a key pathogenic role in PG and canakinumab may represent a therapeutic option for steroid-refractory PG.
Original languageEnglish
JournalBritish Journal of Dermatology
Issue number5
Pages (from-to)1216-1223
Number of pages8
Publication statusPublished - 01.11.2015


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